ViraferonPeg Pen 50, 80, 100, 120 or 150 micrograms powder and solvent for solution for injection in pre-filled pen

1. Name Of The Medicinal Product

ViraferonPeg 50, 80, 100, 120 and 150 micrograms, powder and solvent for solution for injection in pre-filled pen

2. Qualitative And Quantitative Composition

Each pre-filled pen of ViraferonPeg 50, 80, 100, 120 and 150 micrograms contains a sufficient amount of peginterferon alfa-2b as measured on a protein basis in a powder , and the corresponding amount of solvent, to provide 50, 80, 100, 120 and 150 micrograms in 0.5 ml of peginterferon alfa-2b when reconstituted as recommended.

The active substance is a covalent conjugate of recombinant interferon alfa-2b* with monomethoxy polyethylene glycol. The potency of this product should not be compared to that of another pegylated or nonpegylated protein of the same therapeutic class (see section 5.1).

*produced by rDNA technology in E. coli cells harbouring a genetically engineered plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes

Excipients:

ViraferonPeg contains 40 mg of sucrose per 0.5 ml.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Powder and solvent for solution for injection in pre-filled pen.

White powder.

Clear and colourless solvent.

4. Clinical Particulars

4.1 Therapeutic Indications

Adult patients:

ViraferonPeg is indicated for the treatment of adult patients with chronic hepatitis C who are positive for hepatitis C virus RNA (HCV-RNA), including patients with compensated cirrhosis and/or co-infected with clinically stable HIV (see section 4.4).

The best way to use ViraferonPeg in this indication is in combination with ribavirin.

This combination is indicated in naïve patients including patients with clinically stable HIV co-infection and in patients who have failed previous treatment with interferon alpha (pegylated or nonpegylated) and ribavirin combination therapy or interferon alpha monotherapy (see section 5.1).

Interferon monotherapy, including ViraferonPeg, is indicated mainly in case of intolerance or contraindication to ribavirin.

Paediatric patients 3 years of age and older:

ViraferonPeg is indicated in a combination regimen with ribavirin for the treatment of children 3 years of age and older and adolescents, who have chronic hepatitis C, not previously treated, without liver decompensation, and who are positive for HCV-RNA.

When deciding not to defer treatment until adulthood, it is important to consider that the combination therapy induced a growth inhibition. The reversibility of growth inhibition is uncertain. The decision to treat should be made on a case by case basis (see section 4.4).

Please refer also to the ribavirin Summary of Product Characteristics (SPC) for capsules or oral solution when ViraferonPeg is to be used in combination with ribavirin.

4.2 Posology And Method Of Administration

Treatment should be initiated and monitored only by a physician experienced in the management of patients with hepatitis C.

• Dose to be administered

ViraferonPeg should be administered as a once weekly subcutaneous injection. The dose administered in adults depends on whether it is used in combination with ribavirin or as monotherapy.

ViraferonPeg and ribavirin combination therapy

- Adult patients:

ViraferonPeg 1.5 micrograms/kg/week in combination with ribavirin capsules.

The intended dose of 1.5 μg/kg of ViraferonPeg to be used in combination with ribavirin may be delivered in weight categories with the pen/vial strengths according to Table 1. Ribavirin capsules are to be administered orally each day in two divided doses with food (morning and evening).

Table 1 Dosing for combination therapy
Body weight (kg)	ViraferonPeg	Ribavirin capsules
Vial/Pen strength (μg/0.5ml)	Administer once weekly (ml)	Total daily dose (mg)	Number of capsules (200 mg)
< 40	50	0.5	800	4a
40-50	80	0.4	800	4a
51-64	80	0.5	800	4a
65-75	100	0.5	1,000	5b
76-80	120	0.5	1,000	5b
81-85	120	0.5	1,200	6c
86-105	150	0.5	1,200	6c
> 105	150	0.5	1,400	7 d

a: 2 morning, 2 evening

b: 2 morning, 3 evening

c: 3 morning, 3 evening

d: 3 morning, 4 evening

Duration of treatment – Naïve patients

Predictability of sustained virological response: Patients infected with virus genotype 1 who fail to achieve undetectable HCV-RNA or demonstrate adequate virological response at week 4 or 12 are highly unlikely to become sustained virological responders and should be evaluated for discontinuation (see also section 5.1).

• Genotype 1:

- Patients who have undetectable HCV-RNA at treatment week 12, treatment should be continued for another nine month period (i.e., a total of 48 weeks).

- Patients with detectable but

- In the subset of patients with genotype 1 infection and low viral load (< 600,000 IU/ml) who become HCV-RNA negative at treatment week 4 and remain HCV-RNA negative at week 24, the treatment could either be stopped after this 24 week treatment course or pursued for an additional 24 weeks (i.e. overall 48 weeks treatment duration). However, an overall 24 weeks treatment duration may be associated with a higher risk of relapse than a 48 weeks treatment duration (see section 5.1).

• Genotypes 2 or 3:

It is recommended that all patients be treated for 24 weeks, except for HCV/HIV co-infected patients who should receive 48 weeks of treatment.

• Genotype 4:

In general, patients infected with genotype 4 are considered harder to treat and limited study data (n=66) indicate they are compatible with a duration of treatment as for genotype 1.

Duration of treatment - HCV/HIV co-infection

The recommended duration of treatment for HCV/HIV co-infected patients is 48 weeks, regardless of genotype.

Predictability of response and non-response in HCV/HIV co-infection

Early virological response by week 12, defined as a 2 log viral load decrease or undetectable levels of HCV-RNA, has been shown to be predictive for sustained response. The negative predictive value for sustained response in HCV/HIV co-infected patients treated with ViraferonPeg in combination with ribavirin was 99 % (67/68; Study 1) (see section 5.1). A positive predictive value of 50 % (52/104; Study 1) was observed for HCV/HIV co-infected patients receiving combination therapy.

Duration of treatment - Retreatment

Predictability of sustained virological response: All patients, irrespective of genotype, who have demonstrated serum HCV-RNA below the limits of detection at week 12 should receive 48 weeks of therapy. Retreated patients who fail to achieve virological response (i.e. HCV-RNA below the limits of detection) at week 12 are unlikely to become sustained virological responders after 48 weeks of therapy (see also section 5.1).

Retreatment duration greater than 48 weeks in non-responder patients with genotype 1 has not been studied with pegylated interferon alfa-2b and ribavirin combination therapy.

- Paediatric patients 3 years of age and older :

Dosing for children and adolescent patients is determined by body surface area for ViraferonPeg and by body weight for ribavirin. The recommended dose of ViraferonPeg is 60 μg/m²/week subcutaneously in combination with ribavirin 15 mg/kg/day orally in two divided doses with food (morning and evening).

Duration of treatment

• Genotype 1:

The recommended duration of treatment is 1 year. By extrapolation from clinical data on combination therapy with standard interferon in paediatric patients (negative predictive value 96 % for interferon alfa–2b/ribavirin), patients who fail to achieve virological response at 12 weeks are highly unlikely to become sustained virological responders. Therefore, it is recommended that children and adolescent patients receiving ViraferonPeg/ribavirin combination be discontinued from therapy if their week 12 HCV-RNA dropped < 2 log₁₀ compared to pretreatment or if they have detectable HCV-RNA at treatment week 24.

• Genotype 2 or 3:

The recommended duration of treatment is 24 weeks.

• Genotype 4:

Only 5 children and adolescents with Genotype 4 were treated in the ViraferonPeg/ribavirin clinical trial. The recommended duration of treatment is 1 year. It is recommended that children and adolescent patients receiving ViraferonPeg/ribavirin combination be discontinued from therapy if their week 12 HCV-RNA dropped < 2 log₁₀ compared to pretreatment or if they have detectable HCV-RNA at treatment week 24.

ViraferonPeg monotherapy – Adults

As monotherapy the ViraferonPeg regimen is 0.5 or 1.0 μg/kg/week. The lowest vial or pen strength available is 50 μg/0.5 ml; therefore for patients prescribed 0.5 μg/kg/week, doses must be adjusted by volume as shown in Table 2. For the 1.0 μg/kg dose, similar volume adjustments can be made or alternate vial strengths can be used as shown in Table 2. ViraferonPeg monotherapy was not studied in HCV/HIV co-infected patients.

Table 2 Monotherapy dosing
	0.5 μg/kg	1.0 μg/kg
Body weight (kg)	Vial/Pen strength (μg/0.5ml)	Administer once weekly (ml)	Vial/Pen strength (μg/0.5ml)	Administer once weekly (ml)
30-35	50*	0.15	50	0.3
36-45	50*	0.2	50	0.4
46-56	50*	0.25	50	0.5
57-72	50	0.3	80	0.4
73-88	50	0.4	80	0.5
89-106	50	0.5	100	0.5
106-120**	80	0.4	120	0.5
* Must use vial. Minimum delivery for pen is 0.3 ml. ** For patients > 120 kg, the ViraferonPeg dose should be calculated based on the individual patient weight.

Duration of treatment

For patients who exhibit virological response at week 12, treatment should be continued for at least another three-month period (i.e., a total of six months). The decision to extend therapy to one year of treatment should be based on prognostic factors (e.g., genotype, age > 40 years, male gender, bridging fibrosis).

• Dose modification for all patients

If severe adverse reactions or laboratory abnormalities develop during treatment with ViraferonPeg monotherapy or ViraferonPeg in combination with ribavirin, modify the dosages of each product as appropriate, until the adverse reactions abate. As adherence might be of importance for outcome of therapy, the dose should be kept as close as possible to the recommended standard dose. Guidelines were developed in clinical trials for dose modification.

Combination therapy dose reduction guidelines

Table 2a Dose modification guidelines for combination therapy (with ribavirin) based on laboratory parameters
Laboratory values	Reduce only ribavirin daily dose (see note 1) if:	Reduce only ViraferonPeg dose (see note 2) if:	Discontinue combination therapy if:
Haemoglobin	< 10 g/dl	-	< 8.5 g/dl
Adults:Haemoglobin in: Patients with history of stable cardiac disease Children and adolescents: not applicable		< 12 g/dl after four weeks of dose reduction
Leukocytes	-	< 1.5 x 109/l	< 1.0 x 109/l
Neutrophils	-	< 0.75 x 109/l	< 0.5 x 109/l
Platelets	-	< 50 x 109=/l (adults) <70 x 109/l (children and adolescents)	< 25 x 109/l (adults) < 50 x 109/l (children and adolescents)
Bilirubin – direct	-	-	2.5 x ULN*
Bilirubin - indirect	> 5 mg/dl	-	> 4 mg/dl (for > 4 weeks)
Serum Creatinine	-	-	> 2.0 mg/dl
Creatinine Clearance	-	-	Discontinue ribavirin if CrCL < 50ml/min
Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST)	-	-	2 x baseline and > 10 x ULN*   2 x baseline and > 10 x ULN*

^* Upper limit of normal

Note 1: In adult patients 1^st dose reduction of ribavirin is by 200 mg/day (except in patients receiving the 1,400 mg, dose reduction should be by 400 mg/day). If needed, 2^nd dose reduction of ribavirin is by an additional 200 mg/day. Patients whose dose of ribavirin is reduced to 600 mg daily receive one 200 mg capsule in the morning and two 200 mg capsules in the evening.

In children and adolescent patients 1^st dose reduction of ribavirin is to 12 mg/kg/day, 2^nd dose reduction of ribavirin is to 8 mg/kg/day.

Note 2: In adult patients 1^st dose reduction of ViraferonPeg is to 1 µg/kg/week. If needed, 2^nd dose reduction of ViraferonPeg is to 0.5 µg/kg/week. For patients on ViraferonPeg monotherapy: refer to monotherapy dose reduction guidelines section for dose reduction.

In children and adolescent patients 1^st dose reduction of ViraferonPeg is to 40 μg/m²/week, 2^nd dose reduction of ViraferonPeg is to 20 μg/m²/week.

Dose reduction of ViraferonPeg in adults may be accomplished by reducing the prescribed volume or by utilizing a lower dose strength as shown in Table 2b. Dose reduction of ViraferonPeg in children and adolescents is accomplished by modifying the recommended dose in a two-step process from the original starting dose of 60 μg/m²/week, to 40 μg/m²/week, then to 20 μg/m²/week, if needed.

Table 2b Two-step dose reduction of ViraferonPeg in combination therapy in adults
First dose reduction to ViraferonPeg 1 µg/kg	Second dose reduction to ViraferonPeg 0.5 µg/kg
Body weight kg	ViraferonPeg strength to use	Amount of ViraferonPeg (µg) to administer	Volume (ml) of ViraferonPeg to administer	Body weight kg	ViraferonPeg strength to use	Amount of ViraferonPeg (µg) to administer	Volume (ml) of ViraferonPeg to administer
< 40	50 µg per 0.5 ml	35	0.35	< 40	50 µg per 0.5 ml*	20	0.2
40 – 50	45	0.45	40 – 50	25	0.25
51 – 64	80 µg per 0.5 ml	56	0.35	51 – 64	50 µg per 0.5 ml	30	0.3
65 – 75	72	0.45	65 – 75	35	0.35
76 – 85	80	0.5	76 – 85	45	0.45
86 - 105	120 µg per 0.5 ml	96	0.4	86 – 105	50	0.5
> 105	108	0.45	> 105	80 µg per 0.5 ml	64	0.4

* Must use vial. Minimum delivery for pen 0.3 ml

ViraferonPeg monotherapy dose reduction guidelines in adults

Dose modification guidelines for adult patients who use ViraferonPeg monotherapy are shown in Table 3a.

Table 3a Dose modification guidelines for ViraferonPeg monotherapy in adults based on laboratory parameters
Laboratory values	Reduce ViraferonPeg to one-half dose if:	Discontinue ViraferonPeg if:
Neutrophils	< 0.75 x 109/l	< 0.5 x 109/l
Platelets	< 50 x 109/l	< 25 x 109/l

Dose reduction for adult patients who use 0.5 μg/kg ViraferonPeg monotherapy must be accomplished by reducing the prescribed volume by one-half. The 50 μg/0.5 ml vial must be used if necessary since the pen can only deliver a minimum volume of 0.3 ml.

For adult patients who use 1.0 μg/kg ViraferonPeg monotherapy, dose reduction may be accomplished by reducing the prescribed volume by one-half or by utilizing a lower dose strength as shown in Table 3b.

Table 3b Reduced ViraferonPeg dose for the 1.0 μg/kg monotherapy regimen in adults
Body weight (kg)	Target reduced dose (μg)	Vial/Pen strength (μg/0.5ml)	Administer once weekly (ml)	Amount delivered (μg)
30-35	15	50*	0.15	15
36-45	20	50*	0.20	20
46-56	25	50*	0.25	25
57-72	32	50	0.3	30
73-89	40	50	0.4	40
90-106	50	50	0.5	50
> 106	60	80	0.4	64
*Must use vial. Minimum delivery for pen is 0.3 ml.

• Special populations

Use in renal impairment:

Monotherapy:

ViraferonPeg should be used with caution in patients with moderate to severe renal impairment. In patients with moderate renal dysfunction (creatinine clearance 30-50 ml/minute), the starting dose of ViraferonPeg should be reduced by 25 %. Patients with severe renal dysfunction (creatinine clearance 15-29 ml/minute) should have the starting dose of ViraferonPeg reduced by 50 %. Data are not available for the use of ViraferonPeg in patients with creatinine clearance < 15 ml/minute (see section 5.2). Patients with severe renal impairment, including those on hemodialysis, should be closely monitored. If renal function decreases during treatment, ViraferonPeg therapy should be discontinued.

Combination therapy:

Patients with creatinine clearance < 50 ml/minute must not be treated with ViraferonPeg in combination with ribavirin (see ribavirin SPC). When administered in combination with ribavirin, subjects with impaired renal function should be more carefully monitored with respect to the development of anaemia.

Use in hepatic impairment:

The safety and efficacy of ViraferonPeg therapy has not been evaluated in patients with severe hepatic dysfunction, therefore ViraferonPeg must not be used for these patients.

Use in the elderly (

There are no apparent age-related effects on the pharmacokinetics of ViraferonPeg. Data from elderly patients treated with a single dose of ViraferonPeg suggest no alteration in ViraferonPeg dose is necessary based on age (see section 5.2).

Use in paediatric patients:

ViraferonPeg can be used in combination with ribavirin in paediatric patients 3 years of age and older.

4.3 Contraindications

- Hypersensitivity to the active substance or to any interferon or to any of the excipients;

- A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months (see section 4.4);

- Severe, debilitating medical conditions;

- Autoimmune hepatitis or a history of autoimmune disease;

- Severe hepatic dysfunction or decompensated cirrhosis of the liver;

- Pre-existing thyroid disease unless it can be controlled with conventional treatment;

- Epilepsy and/or compromised central nervous system (CNS) function;

- HCV/HIV patients with cirrhosis and a Child-Pugh score

- Combination of ViraferonPeg with telbivudine

Paediatric patients:

- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal ideation or suicidal attempt.

Combination therapy with ribavirin: Also see ribavirin Summary of the Product Characteristics (SPC) if ViraferonPeg is to be administered in combination with ribavirin in patients with chronic hepatitis C.

4.4 Special Warnings And Precautions For Use

Psychiatric and Central Nervous System (CNS): Severe CNS effects, particularly depression, suicidal ideation and attempted suicide have been observed in some patients during ViraferonPeg therapy, and even after treatment discontinuation mainly during the 6-month follow-up period. Other CNS effects including aggressive behaviour (sometimes directed against others such as homicidal ideation), bipolar disorders, mania, confusion and alterations of mental status have been observed with alpha interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with ViraferonPeg be discontinued, and the patient followed, with psychiatric intervention as appropriate. Patients with existence of, or history of severe psychiatric conditions: If treatment with peginterferon alfa-2b is judged necessary in adult patients with existence or history of severe psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and therapeutic management of the psychiatric condition. - The use of ViraferonPeg in children and adolescents with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). Among children and adolescents treated with interferon alfa-2b in combination with ribavirin, suicidal ideation or attempts were reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse events (e.g. depression, emotional lability, and somnolence). Patients with substance use/abuse: HCV infected patients having a co-occurring substance use disorder (alcohol, cannabis, etc) are at an increased risk of developing psychiatric disorders or exacerbation of already existing psychiatric disorders when treated with alpha interferon. If treatment with alpha interferon is judged necessary in these patients, the presence of psychiatric co-morbidities and the potential for other substance use should be carefully assessed and adequately managed before initiating therapy. If necessary, an inter-disciplinary approach including a mental health care provider or addiction specialist should be considered to evaluate, treat and follow the patient. Patients should be closely monitored during therapy and even after treatment discontinuation. Early intervention for re-emergence or development of psychiatric disorders and substance use is recommended.

Growth and development (children and adolescents): During the course of therapy lasting up to 48 weeks in patients ages 3 through 17 years, weight loss and growth inhibition were common (see sections 4.8 and 5.1). The longer term data available in children treated with the combination therapy with standard interferon/ribavirin are also indicative of substantial growth retardation (> 15 percentile decrease in height percentile as compared to baseline) in 21 % of children despite being off treatment for more than 5 years. Case by case benefit/risk assessment in children: The expected benefit of treatment should be carefully weighed against the safety findings observed for children and adolescents in the clinical trials (see sections 4.8 and 5.1). - It is important to consider that the combination therapy induced a growth inhibition, the reversibility of which is uncertain. - This risk should be weighed against the disease characteristics of the child, such as evidence o

Tobramycin and Dexamethasone

Tobramycin and Dexamethasone Ophthalmic Suspension

Sterile

DESCRIPTION

Tobramycin and Dexamethasone Ophthalmic Suspension is a sterile, multiple dose antibiotic and steroid combination for topical ophthalmic use.

The chemical structures for Tobramycin and Dexamethasone are presented below:

Each mL of Tobramycin and Dexamethasone Ophthalmic Suspension contains: Actives: tobramycin 0.3% (3 mg) and dexamethasone 0.1% (1 mg). Preservative: benzalkonium chloride 0.01%. Inactives: tyloxapol, edetate disodium, sodium chloride, hydroxyethyl cellulose, sodium sulfate, sulfuric acid and/or sodium hydroxide (to adjust pH) and purified water.

CLINICAL PHARMACOLOGY

Corticoids suppress the inflammatory response to a variety of agents and they probably delay or slow healing. Since corticoids may inhibit the body's defense mechanism against infection, a concomitant antimicrobial drug may be used when this inhibition is considered to be clinically significant. Dexamethasone is a potent corticoid.

The antibiotic component in the combination (tobramycin) is included to provide action against susceptible organisms. In vitro studies have demonstrated that tobramycin is active against susceptible strains of the following microorganisms:

Staphylococci, including S. aureus and S. epidermidis (coagulase-positive and coagulase-negative), including penicillin-resistant strains.

Streptococci, including some of the Group A-beta-hemolytic species, some nonhemolytic species, and some Streptococcus pneumoniae.

Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus mirabilis, Morganella morganii, most Proteus vulgaris strains, Haemophilus influenzae and H. aegyptius, Moraxella lacunata, Acinetobacter calcoaceticus and some Neisseria species.

Bacterial susceptibility studies demonstrate that in some cases microorganisms resistant to gentamicin remain susceptible to tobramycin.

No data are available on the extent of systemic absorption from Tobramycin and Dexamethasone Ophthalmic Suspension; however, it is known that some systemic absorption can occur with ocularly applied drugs. If the maximum dose of Tobramycin and Dexamethasone Ophthalmic Suspension is given for the first 48 hours (two drops in each eye every 2 hours) and complete systemic absorption occurs, which is highly unlikely, the daily dose of dexamethasone would be 2.4 mg. The usual physiologic replacement dose is 0.75 mg daily. If Tobramycin and Dexamethasone Ophthalmic Suspension is given after the first 48 hours as two drops in each eye every 4 hours, the administered dose of dexamethasone would be 1.2 mg daily.

INDICATIONS AND USAGE

Tobramycin and Dexamethasone Ophthalmic Suspension is indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of bacterial ocular infection exists.

Ocular steroids are indicated in inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe where the inherent risk of steroid use in certain infective conjunctivitides is accepted to obtain a diminution in edema and inflammation. They are also indicated in chronic anterior uveitis and corneal injury from chemical, radiation or thermal burns, or penetration of foreign bodies.

The use of a combination drug with an anti-infective component is indicated where the risk of superficial ocular infection is high or where there is an expectation that potentially dangerous numbers of bacteria will be present in the eye.

The particular anti-infective drug in this product is active against the following common bacterial eye pathogens:

Staphylococci, including S. aureus and S. epidermidis (coagulase-positive and coagulase-negative), including penicillin-resistant strains.

Streptococci, including some of the Group A-beta-hemolytic species, some nonhemolytic species, and some Streptococcus pneumoniae.

Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus mirabilis, Morganella morganii, most Proteus vulgaris strains, Haemophilus influenzae and H. aegyptius, Moraxella lacunata, Acinetobacter calcoaceticus and some Neisseria species.

CONTRAINDICATIONS

Epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and many other viral diseases of the cornea and conjunctiva. Mycobacterial infection of the eye. Fungal diseases of ocular structures. Hypersensitivity to a component of the medication.

WARNINGS

NOT FOR INJECTION INTO THE EYE. Sensitivity to topically applied aminoglycosides may occur in some patients. If a sensitivity reaction does occur, discontinue use.

Prolonged use of steroids may result in glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and posterior subcapsular cataract formation. Intraocular pressure should be routinely monitored even though it may be difficult in pediatric patients and uncooperative patients. Prolonged use may suppress the host response and thus increase the hazard of secondary ocular infections. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. In acute purulent conditions of the eye, steroids may mask infection or enhance existing infection.

PRECAUTIONS

General

The possibility of fungal infections of the cornea should be considered after long-term steroid dosing. As with other antibiotic preparations, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be initiated. When multiple prescriptions are required, or whenever clinical judgement dictates, the patient should be examined with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.

Cross-sensitivity to other aminoglycoside antibiotics may occur; if hypersensitivity develops with this product, discontinue use and institute appropriate therapy.

Information for Patients

Do not touch dropper tip to any surface, as this may contaminate the contents. Contact lenses should not be worn during the use of this product.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No studies have been conducted to evaluate the carcinogenic or mutagenic potential. No impairment of fertility was noted in studies of subcutaneous tobramycin in rats at doses of 50 and 100 mg/kg/day.

Pregnancy

Category C

Corticosteroids have been found to be teratogenic in animal studies. Ocular administration of 0.1% dexamethasone resulted in 15.6% and 32.3% incidence of fetal anomalies in two groups of pregnant rabbits. Fetal growth retardation and increased mortality rates have been observed in rats with chronic dexamethasone therapy. Reproduction studies have been performed in rats and rabbits with tobramycin at doses up to 100 mg/kg/day parenterally and have revealed no evidence of impaired fertility or harm to the fetus. There are no adequate and well controlled studies in pregnant women. Tobramycin and Dexamethasone Ophthalmic Suspension should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Tobramycin and Dexamethasone Ophthalmic Suspension is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 years have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS

Adverse reactions have occurred with steroid/anti-infective combination drugs which can be attributed to the steroid component, the anti-infective component, or the combination. Exact incidence figures are not available. The most frequent adverse reactions to topical ocular tobramycin [TOBREX®* (tobramycin ophthalmic solution)] are hypersensitivity and localized ocular toxicity, including lid itching and swelling, and conjunctival erythema. These reactions occur in less than 4% of patients. Similar reactions may occur with the topical use of other aminoglycoside antibiotics. Other adverse reactions have not been reported; however, if topical ocular tobramycin is administered concomitantly with systemic aminoglycoside antibiotics, care should be taken to monitor the total serum concentration. The reactions due to the steroid component are: elevation of intraocular pressure (IOP) with possible development of glaucoma, and infrequent optic nerve damage; posterior subcapsular cataract formation; and delayed wound healing.

Secondary Infection

The development of secondary infection has occurred after use of combinations containing steroids and antimicrobials. Fungal infections of the cornea are particularly prone to develop coincidentally with long term applications of steroids. The possibility of fungal invasion must be considered in any persistent corneal ulceration where steroid treatment has been used. Secondary bacterial ocular infection following suppression of host responses also occurs.

OVERDOSAGE

Clinically apparent signs and symptoms of an overdosage of Tobramycin and Dexamethasone Ophthalmic Suspension (punctate keratitis, erythema, increased lacrimation, edema and lid itching) may be similar to adverse reaction effects seen in some patients.

DOSAGE AND ADMINISTRATION

One or two drops instilled into the conjunctival sac(s) every four to six hours. During the initial 24 to 48 hours, the dosage may be increased to one or two drops every two (2) hours. Frequency should be decreased gradually as warranted by improvement in clinical signs. Care should be taken not to discontinue therapy prematurely.

Not more than 20 mL should be prescribed initially and the prescription should not be refilled without further evaluation as outlined in PRECAUTIONS above.

HOW SUPPLIED

Sterile ophthalmic suspension in 2.5 mL (NDC 61314-647-25), 5 mL (NDC 61314-647-05) and 10 mL (NDC 61314-647-10) DROP-TAINER®* dispensers.

STORAGE

Store at 8° to 27°C (46° to 80°F).

Store suspension upright and shake well before using.

Rx Only

*TOBREX and DROP-TAINER are registered trademarks of Alcon Research, Ltd.

340032-0608

Distributed by:

FALCON Pharmaceutical, Ltd.

Fort Worth, Texas 76134 USA

Manufactured by:

ALCON LABORATORIES, INC.

Fort Worth, Texas 76134 USA

Printed in USA

Revised: June 2008

PRINCIPAL DISPLAY PANEL

NDC 61314-647-05            Rx Only

FALCON

PHARMACEUTICALS®

Tobramycin and

Dexamethasone

Ophthalmic

Suspension

FOR TOPICAL OPHTHALMIC

USE ONLY

5 mL           STERILE

AFFILIATE OF                     QUALITY RX

ALCON

LABORATORIES, INC.

Tobramycin and Dexamethasone  Tobramycin and Dexamethasone  suspension

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 61314-647 Route of Administration OPHTHALMIC DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TOBRAMYCIN (TOBRAMYCIN) TOBRAMYCIN 3 mg  in 1 mL DEXAMETHASONE (DEXAMETHASONE) DEXAMETHASONE 1 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength TYLOXAPOL   EDETATE DISODIUM   SODIUM CHLORIDE   SODIUM SULFATE   SULFURIC ACID   SODIUM HYDROXIDE   WATER   BENZALKONIUM CHLORIDE   HYDROXYETHYL CELLULOSE (2000 CPS AT 1%)

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 61314-647-25 2.5 mL In 1 BOTTLE None 2 61314-647-05 5 mL In 1 BOTTLE None 3 61314-647-10 10 mL In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA authorized generic	NDA050592	01/02/2009

Labeler - Falcon Pharmaceuticals (874345820)

Registrant - Alcon Laboratories, Inc. (008018525)

Establishment
Name	Address	ID/FEI	Operations
Alcon Laboratories, Inc.		008018525	manufacture

Revised: 07/2011Falcon Pharmaceuticals

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Mission Prenatal

Generic Name: prenatal multivitamins (PRE nay tal VYE ta mins)

Brand Names: Advance Care Plus, Bright Beginnings, Cavan Folate, Cavan One, Cavan-Heme OB, Cenogen Ultra, CitraNatal Rx, Co Natal FA, Complete Natal DHA, Complete-RF, CompleteNate, Concept OB, Docosavit, Dualvit OB, Duet, Edge OB, Elite OB 400, Femecal OB, Folbecal, Folcaps Care One, Folivan-OB, Foltabs, Gesticare, Icar Prenatal, Icare Prenatal Rx, Inatal Advance, Infanate DHA, Kolnatal DHA, Lactocal-F, Marnatal-F, Maternity, Maxinate, Mission Prenatal, Multi-Nate 30, Multinatal Plus, Nata 29 Prenatal, Natachew, Natafort, Natelle, Neevo, Nestabs, Nexa Select with DHA, Novanatal, NovaStart, O-Cal Prenatal, OB Complete, OB Natal One, Ob-20, Obtrex DHA, OptiNate, Paire OB Plus DHA, PNV Select, PNV-Total, PR Natal 400, Pre-H-Cal, Precare, PreferaOB, Premesis Rx, PrenaCare, PrenaFirst, PrenaPlus, Prenatabs OBN, Prenatabs Rx, Prenatal 1 Plus 1, Prenatal Elite, Prenatal Multivitamins, Prenatal Plus, Prenatal S, Prenatal-U, Prenate Advanced Formula, Prenate DHA, Prenate Elite, Prenavite FC, PreNexa, PreQue 10, Previte Rx, PrimaCare, Pruet DHA, RE OB Plus DHA, Renate, RightStep, Rovin-NV, Se-Care, Se-Natal One, Se-Plete DHA, Se-Tan DHA, Select-OB, Seton ET, Strongstart, Stuart Prenatal with Beta Carotene, Tandem OB, Taron-BC, Tri Rx, TriAdvance, TriCare, Trimesis Rx, Trinate, Triveen-PRx RNF, UltimateCare Advance, Ultra-Natal, Vemavite PRX 2, VeNatal FA, Verotin-BY, Verotin-GR, Vinacal OR, Vinatal Forte, Vinate Advanced (New Formula), Vinate AZ, Vinate Care, Vinate Good Start, Vinate II (New Formula), Vinate III, Vinate One, Vitafol-OB, VitaNatal OB plus DHA, Vitaphil, Vitaphil Aide, Vitaphil Plus DHA, Vitaspire, Viva DHA, Vol-Nate, Vol-Plus, Vol-Tab Rx, Vynatal F.A., Zatean-CH, Zatean-PN

What are Mission Prenatal (prenatal multivitamins)?

There are many brands and forms of prenatal vitamin available and not all brands are listed on this leaflet.

Prenatal vitamins are a combination of many different vitamins that are normally found in foods and other natural sources.

Prenatal vitamins are used to provide the additional vitamins needed during pregnancy. Minerals may also be contained in prenatal multivitamins.

Prenatal vitamins may also be used for purposes not listed in this medication guide.

What is the most important information I should know about prenatal vitamins?

There are many brands and forms of prenatal vitamin available and not all brands are listed on this leaflet.

Never take more than the recommended dose of a multivitamin. Avoid taking any other multivitamin product within 2 hours before or after you take your prenatal vitamins. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Many multivitamin products also contain minerals such as calcium, iron, magnesium, potassium, and zinc. Minerals (especially taken in large doses) can cause side effects such as tooth staining, increased urination, stomach bleeding, uneven heart rate, confusion, and muscle weakness or limp feeling. Read the label of any multivitamin product you take to make sure you are aware of what it contains.

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of vitamins A, D, E, or K can cause serious or life-threatening side effects and can also harm your unborn baby. Certain minerals contained in a prenatal multivitamin may also cause serious overdose symptoms or harm to the baby if you take too much.

Overdose symptoms may include stomach pain, vomiting, diarrhea, constipation, loss of appetite, hair loss, peeling skin, tingly feeling in or around your mouth, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine, pale skin, and easy bruising or bleeding.

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may make it harder for your body to absorb certain ingredients of the multivitamin.

What should I discuss with my healthcare provider before taking prenatal vitamins?

Many vitamins can cause serious or life-threatening side effects if taken in large doses. Do not take more of this medication than directed on the label or prescribed by your doctor.

Before taking prenatal vitamins, tell your doctor about all of your medical conditions.

You may need to continue taking prenatal vitamins if you breast-feed your baby. Ask your doctor about taking this medication while breast-feeding.

How should I take prenatal vitamins?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Never take more than the recommended dose of prenatal vitamins.

Many multivitamin products also contain minerals such as calcium, iron, magnesium, potassium, and zinc. Minerals (especially taken in large doses) can cause side effects such as tooth staining, increased urination, stomach bleeding, uneven heart rate, confusion, and muscle weakness or limp feeling. Read the label of any multivitamin product you take to make sure you are aware of what it contains.

Take your prenatal vitamin with a full glass of water.

Swallow the regular tablet or capsule whole. Do not break, chew, crush, or open it.

The chewable tablet must be chewed or allowed to dissolve in your mouth before swallowing. You may also allow the chewable tablet to dissolve in drinking water, fruit juice, or infant formula (but not milk or other dairy products). Drink this mixture right away.

Use prenatal vitamins regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store at room temperature away from moisture and heat. Keep prenatal vitamins in their original container. Storing vitamins in a glass container can ruin the medication.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of vitamins A, D, E, or K can cause serious or life-threatening side effects and can also harm your unborn baby. Certain minerals contained in a prenatal multivitamin may also cause serious overdose symptoms or harm to the baby if you take too much.

Overdose symptoms may include stomach pain, vomiting, diarrhea, constipation, loss of appetite, hair loss, peeling skin, tingly feeling in or around your mouth, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine, pale skin, and easy bruising or bleeding.

What should I avoid while taking prenatal vitamins?

Avoid taking any other multivitamin product within 2 hours before or after you take your prenatal vitamins. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Avoid the regular use of salt substitutes in your diet if your multivitamin contains potassium. If you are on a low-salt diet, ask your doctor before taking a vitamin or mineral supplement.

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may make it harder for your body to absorb certain ingredients of the prenatal vitamin.

Prenatal vitamins side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

When taken as directed, prenatal vitamins are not expected to cause serious side effects. Less serious side effects may include:

• 
  

  upset stomach;

  
  


• 
  

  headache; or

  
  


• 
  

  unusual or unpleasant taste in your mouth.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect prenatal vitamins?

Vitamin and mineral supplements can interact with certain medications, or affect how medications work in your body. Before taking a prenatal vitamin, tell your doctor if you also use:

• 
  

  diuretics (water pills);

  
  


• 
  

  heart or blood pressure medications;

  
  


• 
  

  tretinoin (Vesanoid);

  
  


• 
  

  isotretinoin (Accutane, Amnesteen, Clavaris, Sotret);

  
  


• 
  

  trimethoprim and sulfamethoxazole (Cotrim, Bactrim, Gantanol, Gantrisin, Septra, TMP/SMX); or

  
  


• 
  

  an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Cataflam, Voltaren), indomethacin (Indocin), meloxicam (Mobic), and others.

  
  

This list is not complete and other drugs may interact with prenatal vitamins. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Mission Prenatal resources

• Mission Prenatal Use in Pregnancy & Breastfeeding
• Mission Prenatal Drug Interactions
• Mission Prenatal Support Group
• 0 Reviews for Mission Prenatal - Add your own review/rating

• Cal-Nate MedFacts Consumer Leaflet (Wolters Kluwer)


• CareNatal DHA MedFacts Consumer Leaflet (Wolters Kluwer)


• CitraNatal 90 DHA MedFacts Consumer Leaflet (Wolters Kluwer)


• CitraNatal Assure Prescribing Information (FDA)


• CitraNatal Harmony Prescribing Information (FDA)


• Concept DHA Prescribing Information (FDA)


• Docosavit Prescribing Information (FDA)


• Duet DHA with Ferrazone MedFacts Consumer Leaflet (Wolters Kluwer)


• Folbecal MedFacts Consumer Leaflet (Wolters Kluwer)


• Folcal DHA Prescribing Information (FDA)


• Folcaps Care One Prescribing Information (FDA)


• Gesticare DHA Prescribing Information (FDA)


• Gesticare DHA MedFacts Consumer Leaflet (Wolters Kluwer)


• Inatal Advance Prescribing Information (FDA)


• Inatal Ultra Prescribing Information (FDA)


• Multi-Nate DHA Prescribing Information (FDA)


• Multi-Nate DHA Extra Prescribing Information (FDA)


• MultiNatal Plus MedFacts Consumer Leaflet (Wolters Kluwer)


• Natelle One Prescribing Information (FDA)


• Neevo Caplets MedFacts Consumer Leaflet (Wolters Kluwer)


• Neevo DHA MedFacts Consumer Leaflet (Wolters Kluwer)


• OB Complete 400 MedFacts Consumer Leaflet (Wolters Kluwer)


• Paire OB Plus DHA Prescribing Information (FDA)


• PreNexa MedFacts Consumer Leaflet (Wolters Kluwer)


• PreNexa Prescribing Information (FDA)


• PreferaOB Prescribing Information (FDA)


• Prenatal Plus Prescribing Information (FDA)


• Prenatal Plus Iron Prescribing Information (FDA)


• Prenate Elite Prescribing Information (FDA)


• Prenate Elite MedFacts Consumer Leaflet (Wolters Kluwer)


• Prenate Elite tablets


• Prenate Essential Prescribing Information (FDA)


• PrimaCare Advantage MedFacts Consumer Leaflet (Wolters Kluwer)


• PrimaCare ONE capsules


• PrimaCare One MedFacts Consumer Leaflet (Wolters Kluwer)


• Renate DHA Prescribing Information (FDA)


• Se-Natal 19 Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Se-Natal 19 Prescribing Information (FDA)


• Tandem DHA Prescribing Information (FDA)


• Tandem OB Prescribing Information (FDA)


• TriAdvance Prescribing Information (FDA)


• Triveen-One MedFacts Consumer Leaflet (Wolters Kluwer)


• Triveen-PRx RNF Prescribing Information (FDA)


• UltimateCare ONE NF Prescribing Information (FDA)


• Ultra NatalCare MedFacts Consumer Leaflet (Wolters Kluwer)


• Vinate AZ Prescribing Information (FDA)


• Vitafol-One MedFacts Consumer Leaflet (Wolters Kluwer)


• Zatean-CH Prescribing Information (FDA)

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Where can I get more information?

• Your pharmacist can provide more information about prenatal vitamins.

Acetaminophen/Caffeine/Dihydrocodeine

Pronunciation: a-seet-a-MIN-oh-fen/KAF-een/dye-hye-droe-KOE-deen
Generic Name: Acetaminophen/Caffeine/Dihydrocodeine
Brand Name: Examples include Trezix and Panlor SS

Acetaminophen/Caffeine/Dihydrocodeine contains acetaminophen. Severe and sometimes fatal liver problems, including the need for liver transplant, have been reported with the use of acetaminophen. Most cases of these liver problems occurred in patients taking excessive doses of acetaminophen (more than 4,000 mg per day). Also, patients who developed these liver problems were often using more than 1 medicine that contained acetaminophen. Discuss any questions or concerns with your doctor.

Acetaminophen/Caffeine/Dihydrocodeine is used for:

Relieving moderate to moderately severe pain. It may also be used for other conditions as determined by your doctor.

Acetaminophen/Caffeine/Dihydrocodeine is an analgesic combination. It works in certain areas of the brain and nervous system to decrease pain.

Do NOT use Acetaminophen/Caffeine/Dihydrocodeine if:

• you are allergic to any ingredient in Acetaminophen/Caffeine/Dihydrocodeine or any other codeine- or morphine-related medicine (eg, oxycodone)


• you have severe diarrhea due to taking an antibiotic, severe bowel problems (eg, paralytic ileus), severe asthma, or if you are having an asthma attack


• you are taking naltrexone, quinidine, or sodium oxybate (GHB)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Acetaminophen/Caffeine/Dihydrocodeine:

Some medical conditions may interact with Acetaminophen/Caffeine/Dihydrocodeine. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you drink more than 3 alcohol-containing drinks per day or have a history of alcohol or substance abuse, or suicidal thoughts or behavior


• if you have recently had a head injury or if you have a history of brain injury or tumor, increased pressure in the brain, infection of the brain or nervous system, epilepsy, or seizures


• if you have a history of asthma or other lung or breathing problems, stomach or bowel problems, gallbladder problems (eg, gallstones), or pancreas problems (eg, pancreatitis)


• if you have Addison disease, heart problems, liver problems (eg, hepatitis), an underactive thyroid, prostate problems, kidney problems, urinary problems, or if you have had recent abdominal surgery

Some MEDICINES MAY INTERACT with Acetaminophen/Caffeine/Dihydrocodeine. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Naltrexone because the effectiveness of Acetaminophen/Caffeine/Dihydrocodeine will be decreased and withdrawal symptoms may occur if you are physically dependent on opioids. You must not take naltrexone until you have stopped taking Acetaminophen/Caffeine/Dihydrocodeine for 7 to 10 days and after a naloxone challenge test is negative.


• Quinidine because the effectiveness of Acetaminophen/Caffeine/Dihydrocodeine may be decreased


• Cimetidine, ethanol, HIV protease inhibitors (eg, ritonavir), isoniazid, medicine for mental or mood disorders (eg, olanzapine, haloperidol), medicine for anxiety (eg, diazepam), other narcotic pain medicine (eg, oxycodone), monoamine oxidase (MAO) inhibitors (eg, phenelzine), or sodium oxybate (GHB) because side effects such as excessive drowsiness, disorientation, trouble breathing, or seizures may occur


• Anticoagulants (eg, warfarin) because side effects such as bleeding may be increased by Acetaminophen/Caffeine/Dihydrocodeine

This may not be a complete list of all interactions that may occur. Ask your health care provider if Acetaminophen/Caffeine/Dihydrocodeine may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Acetaminophen/Caffeine/Dihydrocodeine:

Use Acetaminophen/Caffeine/Dihydrocodeine as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Acetaminophen/Caffeine/Dihydrocodeine may be taken with or without food. If stomach upset occurs, take with food to reduce stomach irritation. However, this may decrease its effectiveness.


• If you miss a dose of Acetaminophen/Caffeine/Dihydrocodeine and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Acetaminophen/Caffeine/Dihydrocodeine.

Important safety information:

• Acetaminophen/Caffeine/Dihydrocodeine may cause drowsiness, dizziness, or lightheadedness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Acetaminophen/Caffeine/Dihydrocodeine. Using Acetaminophen/Caffeine/Dihydrocodeine alone, with other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Avoid drinking alcohol or taking other medications that cause drowsiness (eg, sedatives, tranquilizers) while taking Acetaminophen/Caffeine/Dihydrocodeine. Acetaminophen/Caffeine/Dihydrocodeine will add to the effects of alcohol and other depressants. Ask your pharmacist if you have questions about which medicines are depressants.


• Acetaminophen/Caffeine/Dihydrocodeine may cause liver damage. If you drink 3 or more alcohol-containing drinks every day, ask your doctor whether you should take Acetaminophen/Caffeine/Dihydrocodeine or other pain relievers/fever reducers. Alcohol use combined with Acetaminophen/Caffeine/Dihydrocodeine may increase your risk for liver damage.


• When using for an extended period, Acetaminophen/Caffeine/Dihydrocodeine may not work as well and may require different dosing. Talk with your doctor if Acetaminophen/Caffeine/Dihydrocodeine stops working well.


• Acetaminophen/Caffeine/Dihydrocodeine contains acetaminophen. Do not take additional acetaminophen for pain or fever without checking with your doctor or pharmacist. Ask your doctor or pharmacist if you have any questions about which medicines contain acetaminophen.


• Acetaminophen/Caffeine/Dihydrocodeine may cause constipation. To prevent constipation, maintain a diet adequate in fiber, drink plenty of water, and exercise. If you become constipated while taking Acetaminophen/Caffeine/Dihydrocodeine, talk with your doctor or pharmacist. A stool softener or fiber laxative may be required.


• If nausea occurs, consult your doctor or pharmacist about alternatives for decreasing nausea (eg, taking antihistamines, lying down for 1 to 2 hours with minimal head movement).


• To minimize dizziness or lightheadedness, get up slowly when rising from a seated or lying position.


• Caution is advised when using Acetaminophen/Caffeine/Dihydrocodeine in the ELDERLY because they may be more sensitive to the effects of the medicine, especially drowsiness and trouble breathing.


• PREGNANCY and BREAST-FEEDING: If you become pregnant while taking Acetaminophen/Caffeine/Dihydrocodeine, discuss with your doctor the benefits and risks of using Acetaminophen/Caffeine/Dihydrocodeine during pregnancy. Acetaminophen/Caffeine/Dihydrocodeine is excreted in breast milk. Do not breast-feed while taking Acetaminophen/Caffeine/Dihydrocodeine.

When used for long periods of time or at high doses, Acetaminophen/Caffeine/Dihydrocodeine may not work as well and may require higher doses to obtain the same effect as when originally taken. This is known as TOLERANCE. Talk with your doctor if Acetaminophen/Caffeine/Dihydrocodeine stops working well. Do not take more than prescribed.

Acetaminophen/Caffeine/Dihydrocodeine may be habit-forming and lead to DEPENDENCE if used in high doses or for a long period of time. If you are on long-term or high dosage therapy, you may have WITHDRAWAL symptoms (eg, convulsions, tremor, stomach and muscle cramps, vomiting, sweating) if you suddenly stop taking Acetaminophen/Caffeine/Dihydrocodeine. Do not stop therapy abruptly or change dosage without asking your pharmacist or doctor. Discuss overuse with your doctor or pharmacist.

Possible side effects of Acetaminophen/Caffeine/Dihydrocodeine:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Blurred vision; constipation; dizziness; drowsiness; exaggerated sense of well-being; feeling unwell or unhappy; flushing; lightheadedness; mental/mood changes; nausea; nervousness or anxiety; stomach pain; vision changes; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); change in the amount of urine; dark urine; difficulty breathing; slow/irregular breathing; slow/irregular heartbeat; stomach pain; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Acetaminophen/Caffeine/Dihydrocodeine side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include cold, clammy skin; extreme drowsiness; fatigue; loss of consciousness; persistent nausea/vomiting; slow heartbeat; slow, shallow, or abnormal breathing; stomach pain; unusual sweating; weakness; yellowing of the skin or eyes.

Proper storage of Acetaminophen/Caffeine/Dihydrocodeine:

Store Acetaminophen/Caffeine/Dihydrocodeine at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Acetaminophen/Caffeine/Dihydrocodeine out of the reach of children and away from pets.

General information:

• If you have any questions about Acetaminophen/Caffeine/Dihydrocodeine, please talk with your doctor, pharmacist, or other health care provider.


• Acetaminophen/Caffeine/Dihydrocodeine is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Acetaminophen/Caffeine/Dihydrocodeine. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Acetaminophen/Caffeine/Dihydrocodeine resources

• Acetaminophen/Caffeine/Dihydrocodeine Side Effects (in more detail)
• Acetaminophen/Caffeine/Dihydrocodeine Dosage
• Acetaminophen/Caffeine/Dihydrocodeine Use in Pregnancy & Breastfeeding
• Drug Images
• Acetaminophen/Caffeine/Dihydrocodeine Drug Interactions
• Acetaminophen/Caffeine/Dihydrocodeine Support Group
• 8 Reviews for Acetaminophen/Caffeine/Dihydrocodeine - Add your own review/rating

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